Neuronal expression of zinc finger transcription factor REST/NRSF/XBR gene.
The identification of a common cis-acting silencer element, a neuron-restrictive silencer element (NRSE), in multiple neuron-specific genes, together with the finding that zinc finger transcription factor REST/NRSF/XBR could confer NRSE-mediated silencing in non-neuronal cells, suggested that REST/NRSF/XBR is a master negative regulator of neurogenesis. Here we show that, although REST/NRSF/XBR expression decreases during neuronal development, it proceeds in the adult nervous system. In situ hybridization analysis revealed neuronal expression of rat REST/NRSF/XBR mRNA in adult brain, with the highest levels in the neurons of hippocampus, pons/medulla, and midbrain. The glutamate analog kainic acid increased REST/NRSF/XBR mRNA levels in various hippocampal and cortical neurons in vivo, suggesting that REST/NRSF/XBR has a role in neuronal activity-implied processes. Several alternatively spliced REST/NRSF/XBR mRNAs encoding proteins with nine, five, or four zinc finger motifs are transcribed from REST/NRSF/XBR gene. Two of these transcripts are generated by neuron-specific splicing of a 28-bp-long exon. Rat REST/NRSF/XBR protein isoforms differ in their DNA binding specificities; however, all mediate repression in transient expression assays. Our data suggest that REST/NRSF/XBR is a negative regulator rather than a transcriptional silencer of neuronal gene expression and counteracts with positive regulators to modulate target gene expression quantitatively in different cell types, including neurons.
Palm
K
K
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden.
Belluardo
N
N
Metsis
M
M
Timmusk
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D007608:Kainic Acid; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins; D016335:Zinc Fingers / Q000235:genetics*; D000099229:RE1-Silencing Transcription Factor
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007608:Kainic Acid; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099229:RE1-Silencing Transcription Factor; C098679:Xbr-1 protein, Xenopus